Pacritinib in Combination With Low Dose Decitabine in Intermediate-High Risk Myelofibrosis or Myeloproliferative Neoplasm (MPN)/Myelodysplastic Syndrome (MDS)

Sponsor
Washington University School of Medicine
Study ID
NCT02564536
Phase
PHASE1
Status
Withdrawn

Conditions

  • Atypical Chronic Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Juvenile Myelomonocytic Leukemia
  • Myelodysplastic Syndromes
  • Myelofibrosis
  • Myeloproliferative Neoplasm

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Pacritinib — DRUG
    -Patients should take pacritinib at approximately the same times every day with a glass of water, with or without food.
  • Decitabine — DRUG
    -From commercial stock

Study Details

For the first 28 day cycle, all patients will be treated with single agent pacritinib at 200 mg twice daily. The investigators chose this starting dose based on the previous three phase I studies of pacritinib as a single agent which showed that the maximum tolerated dose (MTD) to be 500 mg, and subsequently, the dose of 400 mg daily was recommended for the phase II studies. Recently, the results of the phase III PERSIST-1 trial comparing pacritinib to best available therapy (BAT) in patients with MF was reported at the 2015 American Society of Clinical Oncology (ASCO) annual meeting. Pacritinib was found to be significantly more effective than BAT at reducing spleen volume at 24 weeks of therapy and improving constitutional symptoms. Low dose decitabine has demonstrated depletion of DNMT1 in normal hematopoietic stem cells (HSC) without cytotoxicity and subcutaneous (SC) instead of intravenous (IV) administration may avoid high peak levels that can cause apoptosis. Furthermore, the low toxicity associated with low dose decitabine would allow for more frequent (1 to 3 times weekly) administration of the drug which would catch more cells in S-phase via greater exposure time. Based on these findings, a starting dose of decitabine 5 mg/m2 SC twice weekly should be well tolerated and effective in patients with MF and MPN/MDS syndromes when combined with pacritinib 400 mg daily.

Key Dates

Start date
Jun 30, 2017
Status verified
May 2017
Primary completion
Jun 30, 2020
Completion
Jun 30, 2020

Study Design

Enrollment
0 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Arm 1: Pacritinib and Decitabine
    * Patients will receive one cycle of single agent pacritinib. * Patients who tolerate single agent pacritinib will then receive up to 11 cycles of pacritinib and decitabine combination therapy. * Patients who do not tolerate single agent pacritinib (require dose interruption for more than 7 days before Cycle 2 Day 1) will be considered non-evaluable and replaced. * Pacritinib will be administered orally at a dose of 200 mg twice daily continuously for Days 1 through 28 of a 28-day cycle. * Decitabine will be administered as a subcutaneous injection in clinic on Days 1, 5, 8, 12, 15, 19, 22, and 26 of a 28-day cycle. * Patients may continue treatment for up to 12 cycles.

Primary Outcome Measure

Safety of regimen as measured by adverse events [ Time Frame: 30 days after completion of treatment (up to 1 year) ]

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